Hematopoietins, or hematopoietic growth factors are regulatory proteins that deliver signals between cells of the immune system, and thereby promote the survival, growth and differentiation of hematopoietic cells. These regulatory molecules include all of the colony-stimulating factors (GM-CSF, G-CSF, M-CSF, and multi CSF or interleukin-3), the interleukins (IL-1 through IL-11), the interferons (alpha, beta and gamma), the tumor necrosis factors (alpha and beta) and leukemia inhibitory factor (LIF). These molecules exhibit a wide range of biologic activities with target cells from bone marrow, peripheral blood, fetal liver, and other lymphoid or hematopoietic organs. See, e.g., G. Wong and S. Clark, Immunology Today, 9(5):137 (1988).
The biochemical and biological identification and characterization of certain of these regulatory molecules of the immune system was hampered by the small quantities of the naturally occurring factors available from natural sources, e.g., blood and urine. Many of the hematopoietic molecules have recently been molecularly cloned, heterologously expressed and purified to homogeneity. D. Metcalf, "The Molecular Biology and Functions of the Granulocyte-Macrophage Colony Stimulating Factors," Blood, 67(2):257-267 (1986).! Among these molecules are gamma interferon, human and murine GM-CSF, human G-CSF, human CSF-1 and human and murine IL-3. Several of these purified factors have been found to demonstrate regulatory effects on the hematopoietic and immune systems in vivo, including GM-CSF, G-CSF, IL-3 and IL-2.
There remains a need in the art for additional molecules of therapeutic use which are capable of stimulating or enhancing immune responsiveness for treatment of the wide variety of immune disorders, including e.g., radiation exposure, AIDS, and other disorders characterized by malfunction or disfunction of the immune system.